Effect of COVID-19 mRNA vaccination on COVID-19 severity during Omicron BA.4 and BA.5 predominance periods

In a recent study posted to the medRxiv* preprint server, researchers estimated the association of first-generation messenger ribonucleic acid (mRNA) vaccines (BNT162b2, mRNA-1273) with coronavirus disease 2019 (COVID-19)-related medical encounters.

The researchers performed the study during Omicron BA.4/BA.5 predominance in the United States (US) among immunocompromised adults. Additionally, the researchers compared the epidemiological features and severity of hospitalized COVID-19 cases during the BA.4/BA.5 period with those when Omicron BA.1 and BA.2/BA.2.12.1 were dominant.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 sublineage became predominant in the United States by December 2021. Although BA.1 demonstrated increased transmissibility and evaded COVID-19 vaccine-induced immunity, vaccine booster doses showed the potential to offset a reduction in vaccine effectiveness (VE).

Since then, several more Omicron sub-variants have emerged, including BA.4 and BA.5, which had even greater immune escape potential than BA.1. From June 2022, BA.4 and BA.5 sublineages have become predominant in the US. As new circulating variants of concern (VOCs) emerge, ongoing VE monitoring has become critical for informing public health strategies and policies.

However, the authorization of additional vaccine booster doses and bivalent vaccines in the US in September 2022 has made VE estimations complex. Like first-generation vaccines, bivalent vaccines contain an mRNA component targeting the ancestral virus and a new component targeting the theBA.4/BA.5 spike (S) protein.

Understanding changes in the epidemiology of COVID-19 and VE will inform the interpretation of VE studies for recently authorized bivalent vaccines.

About the study

In the present study, researchers retrieved data from the U.S. Centers for Disease Control and Prevention (CDC) run VISION Network to perform serial assessments of COVID-19 VE in the emergency department (ED)/urgent care (UC). The VISION network covers 268 hospitals, 292 emergency departments, and 140 urgent care clinics across 10 US states.

The team considered two events for the VE analysis – i) ED/UC encounters and hospitalizations with one or more COVID-19-like illness (CLI)-related discharge codes, and ii) a molecular test for SARS-CoV-2 performed within 14 days before BA.4/BA.5 predominant period of June 19 to August 20, 2022.

The study cohort comprised ≥18 years old adults who needed a hospital admission with ≥24 hours duration or multiple hospital admissions within 30 days concerning prior discharge. The team ascertained participants' COVID-19 vaccination status via local immunization information systems (IIS), electronic medical records (EMRs), and claims data.

The researchers used the multivariable logistic regression to estimate the association between symptomatic laboratory-confirmed SARS-CoV-2 infection at an ED/UC encounter or hospitalization and vaccination status. They used the same model to compare the odds of prior receipt of 2, 3, and 4 vaccine doses vs. unvaccinated status in SARS-CoV-2–positive cases vs. SARS-CoV-2–negative controls.

In addition to absolute VE, the team also determined relative VE (rVE) to assess the incremental benefit of receiving an additional vaccine dose. Further, they estimated age-stratified (18–49, 50-64, and ≥65 years) odds ratio (ORs) separately among ED/UC encounters and hospitalizations for any combination of mRNA vaccines.

Study findings

Across all the US states, first-generation COVID-19 vaccines remained effective against COVID-19-associated hospitalization and ICU admission or in-hospital death. However, this protection waned quickly, which showed that the most recent vaccine dose had the greatest impact during the BA.4/BA.5 predominance period.

Regarding epidemiology, cases hospitalized during the BA.4/BA.5 predominance period tended to be less severe than the earlier BA.1 period (64% vs. 36%), although they were eight years older on average.

The estimated VE in recipients of third or fourth doses of an mRNA vaccine against ED/UC visits, hospitalization, and ICU/death was higher than among recipients of two doses but waned during BA.4/BA.5 variant predominance. Additionally, hospitalized cases had a shorter stay and were less likely to be admitted to the ICU or die during the BA.4/BA.5 predominance period.

Intriguingly, these VE estimates hold for both BA.4 and BA.5 sublineages having identical S proteins. These VE estimates also reflect population immunity due to prior infection, although high infection-induced immunity in the unvaccinated or under-vaccinated groups may have blunted these VE estimates.

Conclusions

The study findings provide an important baseline for future VE analyses. The estimated VE was lower during the BA.4/BA.5 predominance period than prior VOCs across all tested outcomes. However, the relative contribution of immune evasion from newer variants vs. other factors, such as the influence of prior infections on VE, was unclear. Also, VE waned over several months with first-generation vaccines. In such cases, approved bivalent booster doses could provide increased protection against BA.4/BA.5; however, this will require future investigation.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.